It is known that magnetic particles (MNPs) are used as heat mediators for the treatment of tumour tissues in magnetically induced hyperthermia treatment1,2,3,4,5,6,7.
Reaching of the treatment temperature (41-45° C.) in the target site is linked to the presence of a high concentration (in the order of grams/liter) of magnetic material in a confined volume8,9. This characteristic obviously cannot be obtained when the tumours are located in parts of the organism that are difficult to reach10.
The use of magnetic nanoparticles has also been proposed for carrying drugs which are released due to the heat generated by exposure of the nanoparticle to an alternating magnetic field11,12,13 (AMF).
Recently, it has been shown that even if irradiation with AMF of the nanoparticles in the vicinity of the tumour cells does not produce heat at macroscopic level, the magnetic nanoparticles are able to induce apoptosis of the tumour cells when exposed to an alternating magnetic field3,14. This effect has been associated with the hypothesis that significant heating occurs only locally, i.e. in the vicinity of the surface of the magnetic nanoparticle15. Furthermore, advantageously, the absence of an increase in the macroscopic temperature reduces the side effects connected with heating of the healthy tissues27,29.
Friedman and collaborators have monitored the local temperature increase in magnetic nanoparticles bound to the surface of some cells, observing the activation of temperature-sensitive TRPV1 ionic channels. These protein, channels allow the inflow of calcium ions from the outside to the inside of the cell if the local temperature reaches values of 40° C.27. Also in this case, although an increase in the flow of calcium ions has been recorded due to activation of the nanoparticles under AMF, no variation has been recorded in the macroscopic temperature.14 
Today, therefore, a reliable system is needed for measuring the local temperature profile of magnetic nanoparticles excited by means of an alternating magnetic field.
The traditional methods for thermal characterisation (for example measurements of the specific absorption rate or SAR) are not suitable for the measurement of localised effects. The first-reason is that said measurements require the performance of experiments with highly concentrated dispersions of nanoparticles in which macroscopic heating of the environment occurs and in which interactions between the particles cannot be ruled out.
Furthermore the definition of SAR is valid only for experiments conducted in conditions near to adiabatic conditions, which are a long way from the isothermal system conditions that occur for a diluted solution in which the heat losses are dominant.
Lastly, the temperature recorded corresponds to the macroscopic temperature of the medium in which the nanoparticles are dispersed rather than to their surface temperature.
Recently temperature mapping strategies have been developed to measure the surface temperature of the nanoparticles16,17.
Jacobsen et al. have reported a method for measuring the molecular temperature based on the dehybridization of double helixes of DNA bound to gold nanoparticles which occurs upon application of an electromagnetic field modulated at radio frequencies18.
This effect has been attributed to local heating of the gold nanoparticles induced by the parasitic currents19.
Kotov et al.30 have developed a molecular thermometer based on an elastic molecular nanosystem assembled on gold nanoparticles and able to measure the local temperature variations. In their system, gold nanoparticles are bound to nanoparticles of CdTe by means of a polymeric spacer which acts as a molecular elastic element (or molecular spring). Since a temperature variation in the range from 20 to 50° C. causes an expansion of the polymer, the exciton-plasmon interaction of the pair of nanocrystals varies, with consequent variation in the fluorescence signal. This system, while guaranteeing a high spatial resolution, has some limitations due to the operating principle: i) the system can be applied only to gold nanoparticles; ii) the variation in the distance between the plasmonic nanoparticle and the semiconductor nanoparticle must fall within a precise range, such as to guarantee the increase in fluorescence. Temperature measurements at the nanoscale have been recently reported also by Carlos et al20. This group has developed a luminescent molecular thermometer based on magnetic nanoparticles coated by silica supports impregnated with rare earth complexes. The temperature dependence of the Tb+3 ion emission line in relation to the Eu3+ ion emission line, which instead remains constant, allows measurement of the absolute temperature in solution with an accuracy of 0.5° C. and in a very wide temperature range, also comprising the physiological range (around 37° C.)20. Furthermore, said system, since it contains magnetic nanoparticles, has been proposed for measuring the temperature in situ and in real time of the surface of magnetic nanoparticles when exposed to hyperthermia treatment, but so far the system has never been applied for said purpose.
In order to measure the temperature at the surface of magnetic nanoparticles, Rinaldi et al.29 have developed a system based on iron oxide coated by a fluorescent polyacrylamide polymer, in which the variation in the fluorescence intensity of the benzofuran-based fluorophore bound to the polymer is correlated with the temperature variation at the surface of the iron oxide exposed to AMF. Following the application of an AMF with appropriate magnetic field frequency and amplitude, the variation in fluorescence intensity of the fluorophore indicates a local temperature at the surface of the nanoparticles higher than 35° C., corresponding to the phase transition temperature of the polymer at the surface of the magnetic nanoparticles. This fluorescence variation occurs also if the macroscopic temperature of the system remains stable at 20° C. When the AMF field is switched off, the temperature of the nanoparticles returns to that of the solution in which they are immersed. In this system, only temperature variations around the transition value, specifically 35° C., can be monitored; it is not possible to measure any temperature profile at the surface of the nanoparticles.
Moreover, all the methods used so far for measuring temperature at the nanoscale are specific for certain types of nanoparticles (for example gold) and therefore cannot be extended to magnetic nanoparticles, or nanoparticles lacking in spatial information. Therefore, the use of said methods does not allow the collection of data useful for mapping the temperature gradients around the nanoparticles exposed to an alternating magnetic field. This information is fundamental for predicting the thermal effects of magnetic nanoparticles subjected to AMF and for designing new therapeutic agents based on magnetic nanoparticles with heat-mediated drug release.